10p deletions
rarechromo.org
10p deletions
A chromosome 10p deletion means that part of one of the body’s chromosomes has
been lost or deleted. If the missing chromosome material contains important
instructions for the body, learning difficulties, developmental delay and health problems
may occur. How serious these problems are depends on how much of the
chromosome has been lost and where the deletion is.
Genes and chromosomes
Our bodies are made up of billions of cells. Most of the cells contain a complete set of
tens of thousands of genes. Genes act like a set of instructions, controlling our growth
and development and how our bodies work.
Genes are carried on microscopically small, thread-like structures called chromosomes.
There are usually 46 chromosomes, 23 inherited from our mother and 23 inherited
from our father, so we have two sets of 23 chromosomes in ‘pairs’.
Apart from two sex chromosomes (two Xs for a girl and an X and a Y for a boy)
the chromosomes are numbered 1 to 22, generally from largest to smallest.
Each chromosome has a short arm (at the top in the picture below) called p from petit,
the French word for small, and a long arm called q (at the bottom). In a 10p deletion,
material has been lost from the short arm of one of the two chromosome 10s.
You cannot see chromosomes with the naked eye, but if you stain them and make their
image about 1,000 times larger with a computer or under a microscope, you can see
that each one has a pattern of light and dark bands.
A small piece or a large piece of the chromosome can be missing. Sometimes it can be
identified under a microscope or on a computer. The missing piece may be so tiny that
it can only be identified using new technology with tests such as FISH or array-CGH.
It is then called a microdeletion. These tests are sometimes used to check if certain
genes are missing and to be more exact about where the chromosome has broken.
One type of deletion is called terminal. The chromosome has broken in one place and
the part of the chromosome from the breakpoint to the end of the arm is missing.
Another type of deletion is called interstitial. There are two breakpoints on the same
arm that have rejoined and the part of the chromosome between them is missing.
Short
arm,
called p
Long
arm,
called q
Two complete
chromosome
10s
2
Chromosome
10p
One 10p
breaking
off
10p15
deletion
How do we know about the effects of a 10p deletion?
Researchers have described around 50 people with a 10p deletion in
medical publications, although there are certainly many more.
When Unique wrote this leaflet, we also had details of 28 members
with a ‘pure’ 10p deletion, without any other chromosome change.
Unique collects regular reports from its member families so we can see
how children and adults develop.
Your genetic specialist can tell you more about the chromosome
material that has been lost. You will almost certainly be given a
karyotype, a shorthand code for your child’s chromosomes that
shows the points where the chromosome has broken and rejoined.
People with a 10p deletion may have the same break in their
chromosomes or a similar one but they do not all have the same
problems or features. There will be differences between your child and
others with apparently similar chromosome changes and these
differences can be quite marked. It is very important to see your child
as an individual and not to make direct comparisons with others.
After all, each of us is unique.
But some features and health problems are similar in people with a
10p deletion. This leaflet describes the things that are similar.
For some specific 10p deletions, little is known and even Unique has few
records. It is hard to be certain then about the effects but as more
people are diagnosed, the picture will hopefully become clearer.
The oldest child with the disorder known to Unique is in her late teens
and the group has one affected adult member, but it is likely that there
are many older people with a 10p deletion.
Sources
and
references
The
information
in this guide
is drawn
partly from
published
medical
research
papers.
We have
focused on
articles
describing
people with a
‘pure’ 10p
deletion,
without any
other
chromosome
change, and
on articles
that include a
review of 10p
10p15 deletions
deletions.
When the breakpoint is in band p15, the deletion may be called
The firstsubtelomeric, meaning that a tiny segment has been lost from very
named author
close to the end of the chromosome. A 10p15 deletion appears to be
and
rare as an isolated finding and is more commonly accompanied by
publication
another change such as the gain of the end of another chromosome
date are given
arm. By early 2007 there were only brief notes and no full descriptions to allow you
in the medical literature of people with a ‘pure’ 10p15 loss but there
to look for
were five reports of people with a simultaneous gain (duplication) from the abstracts
another chromosome. Two of these are related – an aunt and her
or original
niece – and have additional material from chromosome 12p13.2;
articles on
another has a duplication of the tip of 13q; the other has additional
the internet
material from the short arm of chromosome 18 (Battaglia 2007 & 2005; in PubMed. If
Ravnan 2006; Roos 2006; Caliskan 2005). Within Unique’s membership, you wish, you
there are five children and an adult with a ‘pure’ deletion from 10p15
can obtain
and five with additional material from another chromosome arm,
abstracts and
specifically 2q36; 4p15.3; 6p25.3; and 10q26.1.
articles from
With such small numbers, it is not possible to be certain about the
Unique.
effects of a subtelomeric 10p deletion. In particular, no-one can know
3
whether or not there are people who have this deletion but develop normally or
almost normally and are never diagnosed with a chromosome disorder. The picture
that emerges from those with other additional chromosome material is not consistent.
Taking what we know about people who have a ‘pure’ deletion from 10p15, birth
weight at term appears to be low. The pattern of growth after birth is not consistent;
there may be growth delay, as occurs in some other children with chromosome
disorders, but one child of 10 years old is ‘tall but slim’. Feeding problems have been
described in one child, with difficulty latching on to the breast at first and a delay in
moving on from first stage solid foods to lumpier food. In another child unspecified
food intolerances have been described.
As far as development is
Three
concerned, a degree of delay
children
with a
in reaching ‘baby milestones’
10p15
may occur. Babies have
deletion:
learned to roll over between
left, 18
8 and 12 months, to sit
months;
between 10 and 18 months
inset, baby;
and to walk at around two
right,
years, but this may not be
11 years.
possible for all children.
At least three children have a
degree of hypotonia, low
muscle tone that makes the muscles feel floppy but in one child, this was no longer a
major concern by the age of 10. One boy had flat feet and has needed to wear plastic
heel splints to align his ankles and support his feet.
The evidence suggests that these children will need help with their learning and in
particular may well be late in starting to speak and face communication difficulties.
First words have emerged at 3 to 4 years and children have benefited from alternative
means of communication, in particular signing and using pictures both to communicate
needs, ideas and feelings and to signal the sequence of events in a day. At least one child
speaks and signs and has progressed to learning to write, at the age of 7, but this may
not be possible for all.
In terms of behaviour, no particular difficulties have been reported in babyhood.
On the contrary, one baby is described as having a lovely, happy personality. In later
childhood, it appears that more challenging behaviour has emerged and one child has
been described as hyperactive. One child’s challenging behaviour reduced dramatically
when he moved to a residential school with a highly structured environment, clear
routines and a consistent approach.
Unique does not have evidence that as a group these children have consistent medical
needs or birth defects. One child was born with a septal defect (a hole in the heart)
that resolved naturally during the first year of life and a degree of hydrocephalus (water
on the brain) that also resolved naturally within the first year, and one boy had minor
genital problems that could be surgically corrected.
One child had plagiocephaly – an oblique skull shape where one side of the head is
longer than the other, giving it the shape of a parallelogram when viewed from one top;
4
Different
children:
top, 17 months;
below, 11 years.
by the age of 10, this was no longer immediately
noticeable. Another baby with a deletion from
near the tip of 10p was born with early fusion of
the join between the plates of the skull that runs
down the middle of the forehead (metopic suture)
and underwent surgery to re-open the seam to
allow more normal head growth. This child also
had a blockage in the first part of the intestines at
birth, known as duodenal atresia, requiring surgical
correction. The thyroid gland was also small and
the child has hypothyroidism. Another child with a
10p15 deletion was reported to have a low level
of immunity and asthma. Two children developed
seizures that were controlled with medication but
one of them was able to come off medication at
the age of nine without harmful effect.
Deletions from 10p12, 10p13 or 10p14
Among babies and children with a breakpoint at 10p12, 10p13 or 10p14, features such
as some delay in development are consistent and a slow pattern of growth and an
unusual look to the face are common. However, individuals vary widely, both in the
ways they are affected and the severity of the effects. As a broad generalisation, where
the breakpoint is in band 10p14, and especially if the chromosome has broken near to
band 10p15, the effects are milder.
Within band 10p14 there is a gene known as GATA3 and when this gene has been
interrupted or is missing, a child is likely to show one or more of the three hallmark
features of HDR syndrome (pages 13-14). H stands for hypoparathyroidism. Children
often have low calcium levels. D stands for deafness, usually a partial hearing loss that is
present from birth and affects both ears. R is for renal. The
kidneys may be small, abnormal or one may be missing or
there may be urinary tract abnormalities.
A little closer to the centromere (the point where the
short arm meets the long arm) there is a region of 10p
known to be important for the normal development of the
HDR
heart and the cells known as T-cells that help to fight
DGCR2 infections. This region is known as the DiGeorge critical
region 2 (shortened to DGCR2) because babies and
children who have lost important genes from this region
have similar clinical problems to babies with a condition
known as DiGeorge syndrome. However, DiGeorge
syndrome proper is caused by the loss of a tiny amount of
chromosome material from the long arm of chromosome
Approximate position
22. The geneticist or paediatrician who tells you about your
of the region for HDR
child’s chromosome disorder should be able to tell you
syndrome and DiGeorge
syndrome (see text).
whether your child has lost GATA3 or the DGCR2.
5
Appearance
To parents, a baby with a 10p deletion may look little different to other babies.
Nonetheless, you may see familiar features in the pictures in this leaflet and if you meet
another affected family, you may notice some similarities between your child and theirs.
Any similarities are likely to be less easy to interpret if your child has a 10p deletion as
part of a more complex chromosome rearrangement.
10p12 deletion:
2 to 3 years old
10p14 deletion:
6 years old
10p13 deletion:
1 year old
10p13 deletion:
20 months old
10p14 deletion:
11 years old
10p13 deletion:
6 years old
10p13p15 deletion:
5 years old
10p13 deletion:
10 years old
10p14p15.3 deletion:
7 years old
Growth
10p14 It seems that some babies and children with a breakpoint at 10p14 grow slowly
and tend to be short, but this is certainly not true for everyone. Some pregnancies are
normal and ultrasound scans show no growth delay, while in other pregnancies the
baby may be seen to be small for gestational age by the third trimester. Most babies are
born at or slightly before term and the range of birth weights at term is broad – from
2.2kg (4lb 14oz) to 3.75kg (8lb 4oz). Length at birth varies a lot, from one baby who
measured 40cm (16 inches) at 36 weeks to another measuring 52cm (20 inches) at
term. Only one adult has been described – a 26-year-old who was 136cm tall (4’ 6”)
whose small size was noticed as early as the third trimester of pregnancy. Within
Unique’s experience there is one boy whose growth was normal to birth but then tailed
off so that by the age of five he was short for his age and a 10-year-old of normal
height. One child with an interstitial deletion between 10p14 and 10p15.3 was an
average size at birth and remained an average height and weight and was growing well
at 7 years of age (Van Esch 1999; Unique).
10p13 Clinical studies report that babies may be moderately underweight at birth, with
a mean birth weight of 2.44-2.62kg (5lb 6-12oz). The Unique series shows wide
variation, with birth weights at term ranging from 1.474kg (3lb 4oz) to 3.26kg (7lb 3oz).
6
Growth delay appears to continue after birth and most children for whom Unique has
information are short for their age, although proportionate. There is some evidence that
when birth weight is within the normal range, a somewhat faster rate of growth may
continue afterwards. One 10-year-old with a birth length and weight in the normal range
and no important health problems was in the top 10 per cent of the population for height
(Schinzel 2000; Unique).
10p12 The range of birth weights is broad and some babies are born a normal weight.
The recorded range is from 1.93kg (4lb 4oz) to 3.23kg (7lb 2oz). One baby weighed 2.14
kg (4lb 11oz) when born at 35 weeks, falling within the 10th to 25th centiles. Unique has
information on one child, whose growth in early childhood tracked the lowest curves on
the growth chart but followed a normal pattern (Schuffenhauer 1998; Unique).
Feeding
10p14 Many babies do appear to have feeding difficulties in early childhood, but the
severity of any problems varies very much and at least two children with an interstitial
deletion (10p14-15.3; 10p13-15) had no significant feeding difficulties, although
constipation became a long-lasting problem for one. Typically, some babies have a
small lower jaw and receding chin and can find it very hard to latch onto the breast
as newborns. Other features may contribute – such as an unusual shape to the mouth (a
high arched palate) and a relatively immobile tongue.
If specialist feeding support, adapted teats and enriched milks are not enough to ensure
proper weight gain, babies may benefit from temporary feeding direct into the stomach
through a nasogastric tube. Occasionally, babies and older children are most
appropriately fed for some time through a gastrostomy tube direct into the stomach.
Some babies have quite severe and long-lasting gastro oesophageal reflux, where the
stomach contents flush back up the food passage to a significant degree. A baby may
inhale milk, which can cause repeated chest infections. Feed thickeners can be added to
milk to lessen reflux and propping your baby up after a feed can help. Eventually, some
babies outgrow the tendency to bring milk back, but if reflux is severe and persistent, a
surgical operation known as a fundoplication can resolve the problem.
Some babies find it hard to move on to solids or chew and in general self feeding skills
can be late to develop. Older children may continue to find it hard to chew foods and
prefer a soft or mashed diet but Unique’s experience is that most of those who have not
needed a gastrostomy or other surgical intervention are eating family foods and feeding
themselves by school age.
10p13 Feeding problems may be quite marked and can affect both babies with a heart
problem and those without. They may have difficulties coordinating sucking with
swallowing, be reluctant to suck or get very easily tired. Reflux may occur and babies are
then at risk of choking or of inhaling part of their feeds or stomach secretions, setting the
scene for respiratory infections. Some children have much milder feeding problems and
others gradually outgrow their early difficulties and progress to eating ground or blended
solids and eventually to family foods, albeit with delay. More severely affected babies
have benefited in the short or long term from gastrostomy feeding direct to the
stomach, eventually with gradual introduction of oral feeding alongside the
gastrostomy tube (Unique).
7
She still gets respiratory infections due to aspiration of
secretions, but much less frequently and recovers more
rapidly. We often go for months without nasal suction when
it used to be several times a day - age 6
From the age of eight she has eaten almost anything but only
when she wants to. As we believe this is behaviour-related, if
she refuses what is served she has to wait for her next meal.
She is quickly learning to eat at mealtimes - age 10
10p14 deletion,
2 years old
10p13 deletion,
20 months old
10p13p15 deletion,
5 years old
8
10p12 The feeding difficulties described for children with 10p13
and 10p14 deletions appear to affect babies and children with
10p12 deletions, perhaps more severely.
One child began to feed herself from the age of 7.
Sitting, moving, walking
10p14 Babies can be expected to be delayed in reaching their
mobility ‘milestones’, but the evidence from Unique is that the
delay is not usually great. All children known to Unique were
walking before school age.
Some children had a mild degree of hypotonia, the low muscle
tone that leaves muscles feeling loose and the child holding a
‘floppy’ posture, but none needed support for walking.
After wearing splints for a year at age 5 to 6, one child with an
interstitial deletion between 10p14 and 10p15.3 walked, ran and
skipped like her peers and won her school sports day running
race.
Every baby sets his own timetable, but those known to Unique
rolled over between 4 and 12 months, were sitting by 15
months, were on the move - bottom shuffling, scooting or
crawling - by 17 months and started to take independent steps
between 22 months and 3 years and 6 months. Climbing stairs,
running and dancing generally followed but one family remarked
that their son had difficulty integrating both sides of the body
and faced difficulties in actions such as jumping and riding a
bicycle. Another family remarked that their daughter’s feet and
back were painful, despite her good mobility.
Somewhat behind his peers, clumsy and cautious 10p13 As a group, children with a breakpoint at 10p13 seem
to develop somewhat more slowly than children with a 10p14
deletion. As individuals, some children move ahead as fast as a
child with a 10p14 deletion, while others reach their
developmental milestones later. The boy (left) with a 10p13-15
deletion has normal mobility. Low muscle tone is common and
although this improves with increasing mobility, it tends to
persist. Any anatomical anomaly, such as overlapping toes, tends
to delay walking. Once mobile, children may be a danger to
themselves due to their limited understanding of their environment but increasing
physical ability. Unique records show that babies rolled over between 6 and 18 months,
sat alone between 10 and 18 months, and in some cases were on the move around
their second birthday and walking by age 3 to 5 years (in two cases before their second
birthday), although this will not be possible for all. Once children are on the move,
mobility continues to improve, with faster, more independent walking, climbing stairs
and running becoming possible for some. Although walking is possible, some children
will not always walk when required and many families rely on a buggy, stroller or
wheelchair outdoors.
10p12 There is very scant information about mobility in these children. While there is
one report of a child not yet standing at 9 years, Unique has two members who were
walking by the age of 8 (Schuffenhauer 1998; Unique).
Learning
10p14 Children are very likely to need some support with their learning, but how
much help will be needed will only become clear with time. Reports from the medical
literature suggest a generally less optimistic picture than Unique families, in part because
the medical reports are older and children were less likely to receive early stimulation
and intervention. Within the Unique group, there is quite a range of achievement. Two
children are characterised as having severe learning difficulties; one child with a deletion
between 10p14 and p15.3 had a mild to moderate delay at the age of four and by the
age of seven was writing simple sentences, doing simple arithmetic and reading at an
age 5.5 to 6-year equivalent. She was competent with a computer and mouse, having
started at 4 years. Two children, both at early primary age, attended mainstream
schools but learned best when taught 1:1; one of these moved to a special needs
secondary school.
One child had particular facility in reading and was more skilful at writing at a keyboard
than by hand.
He did not reach for toys as a baby, did not babble and was rather passive. He has
presented with sensory dysfunctions from birth: he is oversensitive to movement,
loud sounds and touch. At the age of 5, he is very musical, perceptive and
affectionate; he can draw a face and is learning to write his name. The weak areas for
him are visual/ spatial/ language and memory - age 5
His developmental delay is particularly apparent in speech and language and he has
trouble judging the speed and proximity of objects as well as with spatial awareness.
He started to read and write in his sixth year She loves reading - age 10
10p13 & 10p12
Most children appear to need considerable help with their learning. In addition to their
cognitive difficulties, many have a low muscle tone and the skills of holding and handling
objects develop late. This is not, however, true for all and at least one Unique member
has a moderate learning disability, no hypotonia and good coordination, while a child
with a 10p13-15 deletion was 18 months behind at age 7.
We make sure she feels love, stimulation and has routines to advance at her own
pace - age 3
9
In some ways he is very cute. He doesn’t seem to understand commands but for
example when dinner is being served automatically sits up at the
table - age 4
She seems to learn through mobility and her determination, playfulness, physical
strength and sweetness. She likes to look at picture books and turn pages, but does
not read - age 6
An excellent memory for places, loves the social part of school, music, computers
and physical education but is unable to focus for long periods. She attends a
mainstream school with most of her time in a special education
class - age 10
Communication
Many children who have lost the GATA3 gene from 10p14 will have a hearing loss and
need to wear hearing aids that they can tolerate. With aids, hearing can be improved
and in same cases apparently brought to normal levels.
10p14 Very young children typically use non-verbal communication, smiling, crying,
making vocal noises and pushing or pulling when they want something. Babies and
young children usually have some hearing but they face great difficulties in
understanding speech. Speech and language therapy is very important and from the age
of around three some children learn to sign their needs or use pictures for
communication. Speech may develop in some children, particularly once they are
wearing hearing aids, and its complexity is likely to reflect the child’s general learning
ability. One Unique member had speech apraxia, that is, difficulty saying what he wanted
correctly and consistently and had particular problems with articulation and sequencing.
Treatment of speech apraxia is tailored to the individual and usually calls for frequent
1:1 therapy. By the age of 10, one girl was talking in ‘short, broken down sentences’.
One child with an interstitial deletion between 10p14 and 10p15.3 was communicating
in full sentences by age 7 and although repetitive in her speech and tending to favourite
topics of conversation, was clear to understand, with a vocabulary probably typical of a
5-year-old. Her understanding improved in early childhood so that by age 7, there was
no longer a need to simplify commands. Her vocabulary was still expanding and she
could hold conversations including answering and asking questions, although she quite
often repeated the question.
10p13 & 10p12 Unique’s experience is that older children who have a hearing loss
that was not determined in early babyhood have not usually learned to speak. It is too
early to know whether early diagnosis and intervention will enable youngsters with
10p13 and 10p12 deletions to acquire more than single-word speech. Despite their
lack of speech, children are able to communicate their needs through gesture,
movement and in some cases signing and using pictures. One member with difficulty in
discriminating sounds rather than a hearing impairment has a three word vocabulary by
mid-childhood and communicates chiefly by signing and pictures. At 7 years, a boy with
a 10p13-15 deletion can talk conversationally but has difficulty making many sounds of
speech.
10
Hearing aids: one family’s experience
Hearing is as important as vision to a child with severe to
profound learning difficulties and with an 80 decibel hearing loss on
both sides, our 16-year-old daughter (deletion 10p13 and duplication
5q35.2) needs hearing aids. We started with Behind-the-Ear (BTE)
aids when she was 18 months old but as her outer ears (pinnae) are
small and soft, the casings would not sit flat against her head and
resisted all attempts to restrain them with soft loops or tape. Being
small and floppy, our daughter spent her time rolling on the floor or
propped up. The aids would catch on carpet or textiles and get
pulled out or the tubes would break.
The aid can be seen in When our daughter was three, a visit to a 10p- family with an
place in the ear.
older hearing-impaired child yielded the suggestion of In-the-Ear
(ITE) aids and since then, our daughter has never looked back! With
ITEs, the components are encased within the ear mould and if the manufacturers can
produce a faithful mould from a good impression using a soft material at the canal end, the
aid sits comfortably within the ear. As our daughter is very mobile and still spends much of
her life at floor level, her ITEs are ‘low profile’ so that the knobs do not protrude and catch
on clothing or furniture. The volume control is screwdriver-adjustable so that she does not
adjust the volume when she touches the aid. Drawbacks are that ITEs are more expensive
and problematic to manufacture than BTEs, so take longer to replace. Indeed, we have found
only one manufacturer able to make successful ITEs for our daughter. Also, we cannot give
her an ideal loud volume because with small ears and consequently aids, the close proximity
of amplifier to microphone would cause constant feedback.
However, our daughter loves her hearing aids and is unhappy without them. She tells us
when she wants them in by rubbing her ears and once they are in place, she listens well and
becomes far noisier herself, since then she can hear what she’s ‘saying’! She does flick them
out when tired or irritable or when the batteries go dead and as replacements are not
covered by local insurance, we have to guard against losses.
There are other types of hearing aid available such as body aids where the components are
worn in a bag strapped to the body – useful where higher volume is needed but difficult to
manage for a child with severe learning difficulties. The internet is a good source of
information and you can then discuss the options with your audiologist.
One thing: through aids, all sound is amplified, not just the bits you want to be heard and
even speech is overlaid with electronic ‘noise’. Don’t expect your child to fall in love with
your voice! This could be a reason for trialing the newer, digital hearing aids if you can. Your child’s audiologist will advise on suitable aids. For further information on hearing aids in
the UK, contact the National Deaf Children’s Society on 0808 800 8880 www.ndcs.org.uk
In the US you can contact the Hearing Loss Association of America at www.hearingloss.org
Behaviour
There appears to be no typical behaviour pattern associated with a 10p deletion.
Some children show features of autism or have difficulties with concentration but
these are generally consistent with their level of understanding of the world around
them and in line with their general learning ability.
More than one family has mentioned the emergence of challenging behaviours in
middle childhood. In one case, these proved hard to manage as the triggers changed
rapidly and medication (risperidone) was taken.
11
In another case the challenging and oppositional behaviour
of a child with a 10p15 deletion settled once he was in a
highly structured environment with clear routines and a
consistent approach.
10p13 deletion:
10 years old
10p14
Slow, cautious and hesitant in his actions. Has a very
difficult time with transitions and gets anxious when his
routine is disturbed - age 5
A very independent little girl who knows her own mind.
She has challenging behaviour at times though with patience
it can be managed. Due to her autistic tendencies her play is
immature and repetitive and she can occasionally shout or
hit out at her peers or teachers.
She interacts well but loves her own way and if she doesn’t
achieve this she will scream or hit. Her play is more
immature than her peers which can mean she is left out or
ignored which upsets her. She loves to dance, likes
computer games, jigsaws and playing outdoors - age 7
10p13
Very placid and gentle. He is oblivious of walking over his
younger brother etc but is never deliberately aggressive age 3
Our biggest area of concern at present - age 10
No behaviour problems. She does not get frustrated
because she does not try to do very much - age 15
10p12
Very amiable and happy, loves to be held, hugged and
kissed 10p14 deletion:
11 years old
Medical concerns
HDR syndrome (Barakat syndrome)
The absence of the GATA3 gene located within band 10p14 is known to cause the
three key symptoms of HDR syndrome – hypoparathyroidism, deafness and renal
problems. Research studies so far suggest that around half the babies and children
who have lost the gene will have each of the three symptoms. So a child may have
one, two or all three of the symptoms. Some children, however, have no symptoms
of HDR syndrome.
H - Hypoparathyroidism
Embedded within the thyroid gland at the base of the front of the neck are four
minute hypoparathyroid glands that release a hormone, PTH, whose function is to
regulate the calcium levels in the blood. When the GATA3 gene is missing or
mutated, the glands may not develop completely or they may be missing altogether.
12
This results in hypoparathyroidism and the main effect is an abnormally low level of
calcium in the blood, known as hypocalcaemia.
Babies and children known to have a 10p deletion will have a blood test to show
whether they have hypoparathyroidism. If the tests are positive, treatment will be
started with vitamin D replacement and sometimes calcium. So long as the blood levels
of calcium then return to the normal range, any symptoms should vanish and problems
should not worsen. The calcium can be given as dissolvable granules (or as chewable
tablets) and vitamin D is usually given as drops or capsules of 1-alpha calcidol. This is
the form of vitamin D that the body cannot make without PTH and is needed for
calcium to be absorbed from the gut. Many people only need treatment with 1-alphacalcidol and not with extra calcium. Treatment will be needed for the rest of the child’s
life. The aim of treatment is to keep your child’s blood calcium within the normal range
and to ensure that the ratio between the calcium in the blood and creatinine (a protein
produced by muscle) also stays within the normal range to avoid the risk of calcium
deposits in the kidneys (nephrocalcinosis) and eventual kidney impairment.
At first your child will need frequent blood tests, although this will depend on the
calcium levels when your child was diagnosed and on his or her age. Once the calcium
levels in the blood are stable, blood and urine tests are generally carried out every six
months or so.
It is important to treat hypocalcaemia as early as possible to lessen the impact of any
long term effects. If calcium levels have been too low for a long time before treatment
started there may be some long term effects. Low calcium levels affect the
development and functioning of the brain, so there may be some effects on learning.
If levels of calcium drop low enough to cause repeated and prolonged fits (seizures,
epilepsy), these too can have long-term effects on learning. Low calcium levels can also
affect the functioning of the heart and longstanding hypocalcaemia can result in
cataracts which may need to be surgically removed.
Mild hypocalcaemia is usually symptomless but when it is more severe it is likely to
produce symptoms. This occurs most often when a child is going through a phase of
rapid growth, that is, as a baby and again in adolescence. Symptoms in a baby can be
vague and non-specific. Babies may have tremors, spells when they stop breathing
(apnoeas) and turn blue; they may be lethargic. Any baby who has fits (seizures,
epilepsy), stiffness of the hands or feet and whose breathing is noisy and laboured due
to a spasm of the vocal cords (stridor) should have an urgent measurement of the
calcium level. Older children may develop muscle cramps, tiredness and spasms but
symptoms can also include seizures and stridor.
D - Hearing loss
Of the three hallmark features of HDR syndrome, hearing loss appears to be the most
consistent among children with 10p13 and 10p14 deletions. No child with a ‘pure’
10p15 deletion has had reported hearing loss, but all children with a 10p12 loss who
were tested showed a moderate to severe loss. The cause of the hearing loss is
cochlear degeneration and the loss usually starts before birth as newborn babies
already have an obvious impairment in both ears. This is most obvious for high
frequency sound and is permanent. With time, the hearing loss generally becomes more
marked but with aids, it should be possible to achieve normal hearing levels.
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Many children also get repeated ear infections that can lead to the long term build up of
fluid within the middle ear known as ‘glue ear’. Glue ear causes an intermittent
deafness that has an add-on effect to any permanent hearing loss caused by the 10p
deletion. Glue ear is treated by draining off any excess fluid and inserting tiny
ventilation tubes (grommets) into the eardrum. Although some children are fitted with
grommets, these will not provide a permanent solution and most babies and children
need hearing aids. Most babies also have narrow ear canals which need regular cleaning
to ensure they do not block with wax and can make fitting the aids difficult (van der
Wees 2004; Van Esch 2000; Unique).
R - Renal problems
Once it is known that a baby or child has a 10p deletion, the kidneys and urinary tract
will be checked in the first instance with an ultrasound scan of the bladder and kidneys
and any treatment will depend on what is found.
The kidneys and urinary tract may show abnormalities although the nature of the
defects varies from child to child. The kidneys may be small, one may be missing, there
can be a duplex kidney (where the drainage system forms in duplicate), hydronephrosis
(kidney enlargement, usually due to an obstruction) or urinary reflux, caused when the
urine flushes back from the bladder to the kidneys instead of flowing straight out.
Treatment depends on how severely the kidneys are affected. Very mildly affected
children may only need regular monitoring, while a child who is severely affected may
need kidney dialysis or a transplant (Skrypnyk 2002; Berend 2000; Unique).
Heart problems
Heart conditions have been found in around half of the babies and children with a 10p
deletion reported in the medical literature and it has been suggested that there are
genes around the border of 10p13 and 10p14 that are important for the development
of a healthy heart. This region has been called the DiGeorge 2 region or DGCR2 (CR
stands for critical region). Different heart conditions have been found, most commonly
holes between the two sides of the heart, abnormally formed valves and a blockage in
the blood vessel that takes blood from the heart to the lungs to collect oxygen. The
most common abnormality is a hole between the two upper chambers of the heart
(atrial septal defect, ASD) and recently researchers have pinpointed a segment of 10p14
that may contain genes important for the development of a normal heart. However
even among children who have lost this segment of chromosome 10p, around one baby
in three is born with a normal heart (Yatsenko 2004).
Small holes between each side of the heart usually diminish with time and may close
naturally, but larger holes generally need surgical repair. Unique’s experience has been
that most families do not report a heart anomaly and that many defects do not
interfere with a child’s activities so much that surgical correction is needed.
Generally speaking, children who do need surgery to correct their heart defects
thrive afterwards.
Thymus gland and infections
A 10p deletion can affect the development of the thymus gland. This is a small gland
normally at the base of the neck, where T-cells, one of the groups of white blood cell
that help to fight infection, mature. Some children with a 10p deletion have a very small
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thymus gland, in some children it does not work efficiently and other children may not
have a thymus gland at all. Without a properly functioning thymus, a child cannot
produce normal numbers of T-cells and children may have lower than normal levels of
T-cells. This can mean that infections are slow to clear or are recurrent or both.
Generally as children grow older they are better able to produce T-cells and their
immune system becomes more effective. The thymus is most important early on in life
and as children get older it shrinks.
Some children do have unusually frequent ear, chest and urinary infections, but without
evidence of underlying immunodeficiency.
Minor hand and foot abnormalities
These are quite common and varied but they do not usually have a major impact on
your child. Researchers report features such as incurved fingers and toes or fingers that
overlap or are joined together by a web of skin and tissue; extra fingers; club hand and
foot; broad thumbs; small final finger joints; and fingers that are bent and cannot be
straightened, even by someone else.
Among Unique members, one child with a 10p14 deletion and three out of 10 with a
10p13 deletion had webbed toes (joined by skin and tissue), especially toes 2 and 3; this
affected one out of four children with a 10p12 deletion. The family of one child with a
10p12 deletion reported that he had large thumbs. From the medical literature, one
child with a 10p14 deletion had short arms and another had small hands and feet with
shortened final finger and toe joints (Fryns 1981; Suciu 1983; Unique).
Genital anomalies
Among baby boys, minor genital anomalies are fairly common, regardless of the
breakpoint in 10p. At birth one or both testicles (testes) may not have descended from
the abdomen, where they develop during fetal life, into the scrotum (cryptorchidism).
Regardless of whether they have a chromosome disorder or not, cryptorchidism is
found in about three in 100 baby boys born at term but by the age of one year, 80 per
cent of undescended testes have come down naturally. Treatment for undescended
testicles depends on the suspected cause but whatever the cause, treatment is usually
needed if the testicles do not descend naturally in time. If a hormone problem is
suspected to be the cause, a short course of hormone treatment may be suggested.
Otherwise, or if hormone treatment does not work, the testicles can be brought down
in a short operation under general anaesthetic called an orchidopexy.
Hypospadias may also occur, where the hole through which urine passes is not at the
end of the penis. In addition, all the foreskin may be at the back of the penis with none
at the front and the penis may curve when it is stiff. This can be corrected surgically.
Among girls, one with a deletion between 10p13 and 10p14 was found to have a
duplicated Fallopian tube; a girl with a 10p14 deletion had a developmental defect of
the uterus.
Intestines and bottom
A girl with a 10p14 deletion was born with a malpositioned anus; this was surgically
corrected. Meanwhile for six months she had a colostomy, a surgical operation in which
part of the colon (large intestine) is opened through the wall of the abdomen,
functioning as a substitute anus.
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Two Unique members with a 10p13 deletion experienced pyloric stenosis as young
babies. In this condition the opening between the stomach and the beginning of the
intestines narrows so that milk cannot get through. It affects young babies usually
between two and eight weeks old and causes forceful vomiting. After first treating any
dehydration and mineral imbalances caused by the vomiting, the tight pyloric muscle is
repaired surgically. There are usually no long term effects and the problem is unlikely to
recur.
Seizures
Seizures may occur in children with 10p deletions. One cause is a low level of blood
calcium and vitamin D/calcium replacement prevents this type of seizure from
occurring. Among three children with a ‘pure’ 10p15 deletion and normal calcium
levels, two have experienced seizures, controlled with medication.
Eyesight
There are two typical vision problems associated with untreated 10p deletions but both
are generally avoidable. Ptosis (hooded eyelids) can cause vision problems when they
obscure the pupil and it may be helpful to operate surgically to raise the eyelid.
Untreated hypocalcaemia can also cause cataracts to develop over the lens of the eye
but these do not progress once the low calcium levels are corrected.
Otherwise, no typical vision problems are associated with 10p deletions. However,
individual youngsters have experienced a range of eye conditions. These have not been
reported in children with 10p15 deletions, but among 10 children with 10p14 deletions
two children had blocked tear ducts and three had strabismus (squint). One out of 21
children with a 10p13 deletion was described with strabismus. If strabismus does not
respond to glasses or patching or if these are not possible, it can be corrected surgically
if necessary. Other eyesight problems described in the medical literature but not among
Unique’s membership include abnormally small eyes, Rieger eye malformation (a
collection of abnormalities including a small cornea, an underdeveloped iris and
abnormally joined surfaces at the front of the eye) and degeneration of the retina, the
light-sensitive film at the back of the eye.
Teeth, mouth and jaw
Many children with a 10p deletion have a high palate and a relatively small, receding
lower jaw. In one adult the small size of the jaw became less noticeable with age. Apart
from the difficulties that the small jaw can cause with latching on as a small baby and
later with eating solid foods, it can make the teeth overcrowded so that some need to
be removed and others straightened. Some families have noticed that teeth emerge
with a thinned enamel.
(10p14 deletions: Verri 2004; Yatsenko 2004; Skrypnyk 2002; Van Esch 1999; Kinoshita
1992; Suciu 1983; Bourouillou 1981; Fryns 1981)
(10p13 deletions: Faivre 1999; Schuffenhauer 1998; Sunada 1998; Dasouki 1997;
Hasegawa 1997; Shapira 1994; Greenberg 1993; Kiss & Osztovics 1993; Elstner 1984;
Klep-de Pater 1981)
(10p12 deletions: Schuffenhauer 1998; Hon 1995)
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Interstitial proximal 10p deletions
Two children with
an interstitial
proximal deletion.
Above, at 3 years.
Right, at 12 years.
A loss of material from within a
chromosome means that there are two
breakpoints and is known as an
interstitial deletion. Loss of
chromosome material from bands 10p11
and 10p12 is known as a proximal
deletion. By 2011, 8 children had been
described in the medical literature with a
loss of a segment in this area; Unique has
eight further members, making a total of
16 affected people.
The points where the chromosome has broken vary widely as does the amount of lost
chromosomal material. Microarray diagnoses show losses ranging in size from 1 Mb
(one million base pairs or DNA building blocks) to more than 10 times larger. There is
no obvious link between the size of the deletion and the extent and severity of effects.
The most common features are a delay in development, with a need for learning
support, and some speech delay. However, the extent of delay varies a lot and while
some children are significantly delayed, others are more mildly affected. Many
youngsters learn to sign and the great majority talk, with first words emerging usually in
the third or fourth year. Some go on to speak fluently. A similar range is seen in
mobility skills: children learned to sit between 8 months and 3 years; to crawl around
16-18 months; and to walk between 15 months and 3½ years. Children gradually
learned to climb stairs and to run, albeit in some cases with a clumsy style, their legs
apart, or with a poor sense of balance. One child was not able to walk at 4 years.
Some children but not all had low muscle tone, making them feel floppy to hold as
babies and making it harder and more tiring for them to learn to crawl and walk. Some
children needed leg supports or insoles while walking. A few children had evolving
abnormalities of muscle tone, or showed a mixture of high and low muscle tone in
different parts of the body.
Nine of the children have had episodes of difficult behaviour, most commonly
hyperactivity, autistic-type behaviours and outbursts of aggression. They have generally
responded well to medication for their difficult behaviours. Three children have also
had very disturbed sleep and needed medication such as melatonin.
Feeding presented difficulties for 5 newborn babies but apart from one, who had a split
in the soft palate at the back of the mouth and reflux (bringing feeds back) and had a
feeding tube placed direct into the stomach, feeding was normal once past early
babyhood. Three of these 5 babies and 1 other also had significant constipation, treated
with stool softeners.
Before birth, babies generally grew normally, although birth weights at term ranged
from 1.92 kg (4lb 4oz), well down in the lowest 3 per cent of newborn babies, to 3.645
kg (8lb 1oz), in the top 60 per cent. Growth in babies and children varied quite widely,
with some children significantly short for their age, some short, some of a normal
height and one at the upper limit of normal.
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As far as their health was concerned, the most common difficulty for more than half the
babies was a heart problem. Five babies had holes between the lower, pumping
chambers of the heart (ventricular septal defects/ VSDs), sometimes as the only
problem, sometimes linked with other heart problems. At least one baby needed open
heart surgery to close the VSDs, but thrived well afterwards. Four babies were born
with a persistent ductus arteriosus. This occurs when a normal short cut in the
circulation of an unborn baby fails to close naturally soon after birth. In 2 babies it
closed on its own; the other two needed surgery. Two babies had a significant
narrowing of the aorta, the blood vessel that leads from the heart to the rest of the
body, requiring surgery to widen it. Two babies had a problem with one of the valves in
the heart, in one case the pulmonary valve through which blood passes on its way to
the lungs, in the other case the aortic valve which regulates blood flow into the aorta.
Ten children have some kind of vision defect. Four have a squint (strabismus), 3 have an
astigmatism (an abnormal curvature of the cornea at the front of the eye); 2 have
amblyopia (a ‘lazy eye’, where the brain prefers one eye to the other); 2 are short
sighted, 1 is long sighted and one child has long sight in one eye and short sight in the
other; 1 child has a developmental defect of structures at the back of the eye and
underdevelopment of the front part of both eyes; and 2 children are visually impaired in
one eye.
Six children have some hearing loss. In 2 children the hearing impairment is caused by
glue ear, so is temporary, in a third child, glue ear contributes, but in 4 children, there is
a degree of permanent sensorineural impairment. In one teenager, hearing got
progressively worse until she had a profound impairment.
Three children have had seizures, although one newborn baby had a single seizure
shortly after birth. The brains of 8 children, including 2 who had seizures, were found
to have some unusual structure: 2 children had a thin or underdeveloped corpus
callosum (the band of nerve fibres linking the two sides of the brain); 2 had an
underdevelopment of the cerebellum part of the brain; 3 had somewhat enlarged fluidfilled spaces within the brain; 1 had a mild degree of hydrocephalus (accumulation of
fluid); 3 had cysts; 1 had abnormal slits or clefts in the cerebral hemispheres of the
brain, known as schizencephaly; and one had a skull with the appearance of beaten
copper.
Two/7 baby boys were born with one or both their testicles not yet descended into
the scrotum. Other problems affect individual children: one baby was born with a
blockage of one nasal passage and of part of the sinuses; another had had defects in the
formation of the anus, with a stenosis (narrowing) and a channel linking the anus with
the vagina; another with a failure of the collar bone to form properly; one has coeliac
disease; another has an extra rib and hypothyroidism, treated with thyroxine; and one
child has inguinal hernias.
(Yatsenko 2004; Shahdadpuri 2008; Wentzel 2011; Unique).
For the seven children described in the medical literature with one breakpoint in band
p11 or p12 and the second in band p13, information is limited because only clinical
descriptions are available. In general, clinical descriptions focus on problems rather than
areas of normality or strength. From what is known, it seems that most children, if not
all, would need support with their learning; one child was described as having a
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moderate difficulty with learning at the age of seven. Speech and language may also
emerge late; one child spoke his/her first words at the age of four. Baby milestones were
also likely to be delayed; one child sat at 12 months and walked at two years.
Information on growth does not appear consistent. Two babies were born small for their
gestational age, while another was an average weight at birth and continued to grow at a
normal rate.
Minor anomalies of the hands and feet were common. Four children had either broad
thumbs, contracted fingers, incurving fifth fingers or an underdeveloped nail on the fifth
finger and two children had webbed or broad toes.
In terms of possible birth defects and general health, the most common problem was a
heart defect and specifically an ASD (see page 14), found in four out of seven children.
Two children had a cleft (split) in the soft palate at the back of the mouth and one also
had a cleft lip. One child had a permanent hearing loss in both ears.
(Firouzabadi 2005; Yatsenko 2004; Schuffenhauer 1998; Kato 1996; Lipson 1996; Pignata
1996; Obregon 1992,1)
Why did the 10p deletion occur?
Some 10p deletions are the result of a rearrangement in one parent’s chromosomes. This
is usually a balanced translocation in which material has changed places between
chromosomes but no material has been lost or gained and the parent usually has no
difficulties with health or development. Occasionally, when the deletion is very small, one
parent has the same deletion as the child. A blood test to check the parents’
chromosomes will show what the situation is.
Most 10p deletions occur when both parents have normal chromosomes. The term that
geneticists use for this is de novo (dn). De novo 10p deletions are caused by a change
that has usually occurred when the parents’ sperm or egg cells were formed or less
commonly around the time of conception.
Children from all parts of the world and from all types of background have 10p deletions.
No environmental, dietary, workplace or lifestyle factors are known to cause them.
There is nothing that either parent did before or during pregnancy that can be shown to
have caused the deletion and equally nothing could have been done to prevent it. So noone is to blame or at fault.
Can it happen again?
The possibility of having another pregnancy with a 10p deletion depends on the parents’
chromosomes. If both parents have normal chromosomes, the 10p deletion is very
unlikely to happen again.
If a blood test shows that either parent has a chromosome change involving 10p, the
possibility is increased of having other pregnancies with chromosome changes. Usually
one parent has a balanced translocation. Occasionally one parent has the same
chromosome change as the child.
Once the family chromosome change or translocation is known, a test can be done in any
future pregnancy to find out whether the baby’s chromosomes are affected. Discussing
the chromosome change with other family members gives them the opportunity to have
a blood test to see if they too carry it.
A genetic specialist can give you more guidance for your family.
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Support and Information
Rare Chromosome Disorder Support Group,
G1, The Stables, Station Road West, Oxted, Surrey RH8 9EE, United Kingdom
Tel/Fax: +44(0)1883 723356
[email protected] I www.rarechromo.org
Join Unique for family links, information and support.
Unique is a charity without government funding, existing entirely on donations
and grants. If you can, please make a donation via our website at
www.rarechromo.org Please help us to help you!
This information guide is not a substitute for personal medical advice. Families should
consult a medically qualified clinician in all matters relating to genetic diagnosis,
management and health. Information on genetic changes is a very fast-moving field and
while the information in this guide is believed to be the best available at the time of
publication, some facts may later change. Unique does its best to keep abreast of
changing information and to review its published guides as needed. It was compiled by
Unique and reviewed by Dr Hilde Van Esch, MD, PhD, Center for Human Genetics, Leuven,
Belgium and by Unique’s chief medical advisor, Professor Maj Hultén BSc PhD MD
FRCPath, Professor of Reproductive Genetics, University of Warwick, UK. 2007 Revison
2011 (PM)
Copyright © Unique 2011
Rare Chromosome Disorder Support Group Charity Number 1110661
Registered in England and Wales Company Number 5460413
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